Exposure assessment studies published to date have not included biomarker analysis of isocyanurate (an oligomer of 1,6-hexamethylene diisocyanate) exposure, which constitutes the greatest inhalation and skin exposure in spray painters. Further, the sensitization capacity of isocyanurate is greater than 1,6- hexamethylene diisocyanate monomer (HDI) or HDI biuret. We propose to investigate and determine how individual and environmental factors affect isocyanurate and HDI monomer exposure-biomarker associations in our well-characterized worker population of spray painters. To achieve our goal, we will utilize quantitative measures of inhalation and dermal exposure and biomarker levels over multiple independent sampling visits as well as sophisticated exposure modeling that will allow us to link the observed biomarker levels to other predictors of systemic exposure such as personal and workplace factors. Through this approach, we will obtain quantitative data that will distinguish between isocyanurate and HDI monomer exposure and, thus, provide a major advance in characterizing both isocyanurate and HDI monomer exposures through multiple exposure routes. Demonstration and quantification of sources of individual differences in systemic exposure will significantly contribute to establishing realistic exposure-dose relationships. This proposed research project, to our knowledge, represents the first comprehensive study to measure both HDI monomer and its oligomer isocyanurate exposures and their specific metabolites as biomarkers in exposed workers. The data obtained will fill major data gaps within the exposure-biomarker relationship continuum regarding HDI oligomer and monomer exposures and, thus, will significantly contribute towards realistic exposure assessment for spray painters who have an increased risk of developing isocyanate-related adverse health effects. This research project will benefit two NIOSH NORA sectors: Services (Automotive Body, Paint, and Interior Repair and Maintenance) and Manufacturing (Paint, Coating, and Adhesive Manufacturing) by providing critical new information on isocyanurate and HDI monomer exposures as well as on factors affecting individual differences in exposure and biomarker levels. This research may also allow us to provide useful input in setting exposure limits by taking into account the individual variation in exposure and biomarker levels to both isocyanurate and HDI monomer.